Regulation of Bcl-3 through interaction with the Lck tyrosine kinase.

bcl-3 is a protooncogene which undergoes chromosomal translocation in a subset of chronic B-cell lymphocytic leukemia cells. Bcl-3 is a unique IkappaB family protein that regulates transcription of a number of NF-kappaB target genes through interactions with NF-kappaB dimers. Based on previous studies, suggesting that Bcl-3 interacts with the Fyn tyrosine kinase in platelets, we investigated possible interactions of Bcl-3 with Lck, a related tyrosine kinase important in lymphoid cells. Protein-protein interactions between Bcl-3 and the Lck tyrosine kinase were identified both in vitro and in vivo. Lck enhanced Bcl-3-mediated activation of a p52/Bcl-3-responsive promoter in reporter gene assays independent of its tyrosine kinase activity, but requiring the Lck SH3 protein interaction domain. These studies suggest that Bcl-3 might participate in oncogenic pathways involving Lck.